School’s published research again receives high marks in 20207 min read

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Ann Arbor, Mich., Jan. 8, 2021 – With nearly $26 million in annual research expenditures, the University of Michigan School of Dentistry is involved in a wide range of scientific research that includes new biomaterials, regenerative medicine and insights into cancer that are helping to unlock new breakthroughs.

This significant research by faculty and staff is highlighted each year in leading scientific journals, helping to promote the development of new knowledge in the oral health sciences and related fields that contribute to improved health for people around the country and the world.

Research is a vital component of the school’s mission of “advancing health through education, service, research and discovery,” said Vesa Kaartinen, Associate Dean for Research. “Documenting and promoting basic, translational, clinical and health services research, along with associated educational programs, is our intent. We want to encourage discoveries and their implementation into practice. This effort can be seen is the range, diversity and significant output of literature our faculty publish each year.”

In 2020, the school’s faculty published 207 papers, articles and reviews. Here are some of the top papers, based on overall impact, with links to their PubMed abstracts:

• Advanced Functional Materials: Biodegradable nanofibrous temperature-responsive gelling microspheres for heart regeneration.  This paper describes the development of a new copolymer and its self-assembly into nanofibrous gelling microspheres that can help restore heart cells and muscles after a heart attack. The capability of maintaining 3D geometry after injection and the transplantation of embryonic stem cell-derived heart muscle cells carried by the microspheres led to a striking ten-fold graft size increase over direct heart cell injections in an infarcted rat model, which is the highest reported engraftment to date. These novel microspheres may also serve as advanced injectable and integrative biomaterials for cell/biomolecule delivery in a variety of biomedical applications.  Authors: Peter Ma, et al.
• Nature Communications: A Wnt-mediated transformation of the bone marrow stromal cell identity orchestrates skeletal regeneration. This paper examines how specialized dormant stromal cells in the bone marrow are activated in response to injury and during regeneration to transform into cells that will form bone in association with specific cellular events termed canonical Wnt signaling. This elegant study highlights a unique mechanism by which dormant cells are enlisted for regeneration of bone.  Authors: Noriaki Ono, Wanida Ono, Yuki Matsushita, et al.
• Journal of Clinical Investigation:  HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING. This study utilized multiple methodologies to derive new insights into head and neck tumor development associated with human papillomavirus (HPV). This paper reports a striking and potent mechanism that HPV utilizes to shut down the innate immune system and avoid being targeted by immune cells.  HPV16, which is an HPV subtype that drives over 90 percent of the HPV-positive head and neck squamous cell carcinoma, encodes a protein, termed E7, to induce tumor cell proliferation. A previously unknown function of HPV16 E7 was found in promoting the degradation of a central molecule that activates the innate type-I interferon response.  This mechanism has potential for further exploitation in restoring cancer immunogenicity.  Authors: Yu Leo Lei, Peter Polverini, Christopher Donnelly, Xiaobo Luo, et al.
• Biomaterials:  Nanofibrous spongy microspheres for the delivery of rabbit mesenchymal stem cells and anti-miR-199a to regenerate nucleus pulposus and prevent calcification.  Lower back pain is mainly caused by intervertebral disc degeneration, in which calcification is frequently involved. This paper describes how novel nanofibrous spongy microspheres can be used to carry rabbit bone marrow mesenchymal stromal cells (MSCs) to regenerate nucleus pulposus tissues. These microspheres significantly enhanced MSC seeding, proliferation and differentiation over control microcarriers. Results demonstrated a system to promote the nucleus pulposus phenotype that resisted calcification and rescued intervertebral disc function. Authors: Peter Ma, Ganjun Feng, et al.
• ACS Applied Materials & Interfaces: Injectable MMP-Responsive Nanotube-Modified Gelatin Hydrogel for Dental Infection Ablation. This paper presents a novel on-demand system for delivering chlorhexidine in a root canal with an injectable, biodegradable and biocompatible hydrogel. The drug delivery mechanism is based on the degradation of a photocrosslinkable gelatin methacryloyl hydrogel and subsequent release of a potent antimicrobial with minimal toxicity. This study provides promise for a new clinical strategy for dental infection ablation. Authors: Marco Bottino, Christopher Fenno, Juliana Ribeiro, et al.
• ACS Applied Materials & Interfaces: Three-Dimensional Electrodeposition of Calcium Phosphates on Porous Nanofibrous Scaffolds and Their Controlled-Release of Calcium for Bone Regeneration.  To mimic the bone matrix of mineralized collagen and to impart a microporous structure to facilitate cell migration and bone regeneration, this paper describes the development of a nanofibrous polymer scaffold with highly interconnected pores and three-dimensional calcium phosphate coating utilizing an electrodeposition technique. The mineral content, morphology, crystal structure, and chemical composition could be tailored by adjusting the deposition temperature, voltage, and duration. This permineralized nanofibrous scaffold enhanced bone regeneration greater than the control scaffold and was associated with released calcium ions and bone cell proliferation.  Authors: Peter Ma, Laurie McCauley, Xue Mi, et al.
• ACS Applied Materials & Interfaces: Extracellular Matrix/Amorphous Magnesium Phosphate Bioink for 3D Bioprinting of Craniomaxillofacial Bone Tissue.  This paper focuses on the development of a tissue-specific bioink consisting of an extracellular matrix hydrogel and amorphous magnesium phosphate microparticles that enables plotting of 3D constructs with high shape fidelity and osteogenic potential. In vitro results demonstrated significant improvement in mineralized tissue formation of the cell-laden 3D constructs. When implanted in a cranial model of bone regeneration, cell-free constructs with amorphous magnesium phosphate enhanced bone formation confirming the potential of translating this bioink toward the regeneration of patient-specific craniomaxillofacial bone defects. Authors: Marco Bottino, Nileshkumar Dubey, et al.
• Acta Biomaterialia: Highly tunable bioactive fiber-reinforced hydrogel for guided bone regeneration. The paper describes development of next-generation guided bone regeneration membranes with tunable mechanical and therapeutic properties to amplify bone regeneration in compromised sites. The fiber-reinforced hydrogel membrane showed favorable cellular responses, significantly higher rates of mineralization, upregulation of bone forming genes and mineralized tissue formation. The presence of poly(Ɛ-caprolactone) fiber meshes fabricated via melt electrowriting delayed degradation of the hydrogel and prevented soft tissue invasion into the defect.  Authors: Marco Bottino, Arwa Daghrery, Nileshkumar Dubey, et al.
• Journal of Bone and Mineral Research: FAK Promotes Early Osteoprogenitor Cell Proliferation by Enhancing mTORC1 Signaling. Focal adhesion kinase (FAK), a protein involved in how cells stick to each other and their surroundings, plays important roles in bone health and disease such as osteoporosis but the underlying mechanisms are not clear. This paper shows that mice lacking FAK in early osteoprogenitor cells exhibited low bone mass and low numbers of bone forming cells.  In contrast, mice lacking FAK in more mature osteoblast cells did not have bone loss. The data derived suggest that FAK promotes early osteoprogenitor cell proliferation by enhancing a specific type of signaling (mammalian/mechanistic target of rapamycin complex 1 signaling). The loss of FAK in osteoblasts could be compensated by an upregulated active proline-rich tyrosine kinase 2, which belongs to the same tyrosine kinase family as FAK.  Authors: Fei Liu, Shuqun Qi, et al.

To highlight research by faculty and staff, the school holds an annual Research Day. This year’s virtual event will be held on Thursday, Feb. 18, and includes research presentations and a keynote address by Dr. Arlyne B. Simon, platform architect at Intel Corporation and noted biomedical engineer, author and entrepreneur. More information on Research Day is available on the Research Office website here.

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The University of Michigan School of Dentistry is one of the nation’s leading dental schools engaged in oral health care education, research, patient care and community service.  General dental care clinics and specialty clinics providing advanced treatment enable the school to offer dental services and programs to patients throughout Michigan.  Classroom and clinic instruction prepare future dentists, dental specialists and dental hygienists for practice in private offices, hospitals, academia and public agencies.  Research seeks to discover and apply new knowledge that can help patients worldwide.  For more information about the School of Dentistry, visit us on the Web at: www.dent.umich.edu.  Contact: Lynn Monson, associate director of communications, at dentistry.communications@umich.edu, or (734) 615-1971.